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使用缺氧评分识别黑色素瘤预后预测特征

Identification of Signatures of Prognosis Prediction for Melanoma Using a Hypoxia Score.

作者信息

Shou Yanhong, Yang Lu, Yang Yongsheng, Zhu Xiaohua, Li Feng, Xu Jinhua

机构信息

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Institute of Dermatology, Shanghai, China.

出版信息

Front Genet. 2020 Sep 29;11:570530. doi: 10.3389/fgene.2020.570530. eCollection 2020.

Abstract

Melanoma is one of the most aggressive cancers. Hypoxic microenvironment affects multiple cellular pathways and contributes to tumor progression. The purpose of the research was to investigate the association between hypoxia and melanoma, and identify the prognostic value of hypoxia-related genes. Based on the GSVA algorithm, gene expression profile collected from The Cancer Genome Atlas (TCGA) was used for calculating the hypoxia score. The Kaplan-Meier plot suggested that a high hypoxia score was correlated with the inferior survival of melanoma patients. Using differential gene expression analysis and WGCNA, a total of 337 overlapping genes associated with hypoxia were determined. Protein-protein interaction network and functional enrichment analysis were conducted, and Lasso Cox regression was performed to establish the prognostic gene signature. Lasso regression showed that seven genes displayed the best features. A novel seven-gene signature (including ABCA12, PTK6, FERMT1, GSDMC, KRT2, CSTA, and SPRR2F) was constructed for prognosis prediction. The ROC curve inferred good performance in both the TCGA cohort and validation cohorts. Therefore, our study determined the prognostic implication of the hypoxia score in melanoma and showed a novel seven-gene signature to predict prognosis, which may provide insights into the prognosis evaluation and clinical decision making.

摘要

黑色素瘤是最具侵袭性的癌症之一。缺氧微环境影响多种细胞通路并促进肿瘤进展。本研究的目的是探讨缺氧与黑色素瘤之间的关联,并确定缺氧相关基因的预后价值。基于基因集变异分析(GSVA)算法,利用从癌症基因组图谱(TCGA)收集的基因表达谱来计算缺氧评分。Kaplan-Meier曲线表明,高缺氧评分与黑色素瘤患者较差的生存率相关。通过差异基因表达分析和加权基因共表达网络分析(WGCNA),共确定了337个与缺氧相关的重叠基因。进行了蛋白质-蛋白质相互作用网络和功能富集分析,并进行Lasso Cox回归以建立预后基因特征。Lasso回归显示七个基因具有最佳特征。构建了一个新的七基因特征(包括ABCA12、PTK6、FERMT1、GSDMC、KRT2、CSTA和SPRR2F)用于预后预测。ROC曲线在TCGA队列和验证队列中均显示出良好的性能。因此,我们的研究确定了缺氧评分在黑色素瘤中的预后意义,并展示了一种新的七基因特征来预测预后,这可能为预后评估和临床决策提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adff/7550673/78ee3941e9ca/fgene-11-570530-g001.jpg

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